The goal of this study is to evaluate the efficacy and tolerability of prednisone in patients with newly diagnosed ocular myasthenia whose symptoms have failed to remit in response to a trial of cholinesterase inhibitor therapy with pyridostigmine. The selection of prednisone as the therapeutic agent is based on its broad immune suppressive mechanism of action, strong preliminary data that a modest dosage of prednisone (together with pyridostigmine) is substantially more effective than pyridostigmine alone, and that attention to the risk of adverse effects and the initiation of appropriate prophylactic and therapeutic measures can mitigate most of these adverse effects. Prednisone may have the added advantage of reducing the risk of progression to generalized myasthenia gravis (GMG). This will be a double-blind trial in which patients whose symptoms do not remit on pyridostigmine alone will be randomized to receive either placebo or a gradually escalating dose of prednisone in conjunction with a stable dose of pyridostigmine. The dosage of prednisone will be adjusted based on combined metrics of tolerability and efficacy. The double-blind treatment phase will extend over four months, after which patients who have still not achieved remission will receive rescue therapy with high dose prednisone (followed by a gradual taper) in an open-label fashion. The primary endpoint for the double-blind phase will be the proportion of subjects in each group who fail treatment, where treatment failure is defined as a lack of efficacy (i.e. failure to achieve sustained minimal manifestation status within four months of therapy) or the presence of toxicity (i.e., the occurrence of side effects that lead to discontinuation of prednisone). This outcome is useful because it combines measures of efficacy and tolerability, and is clinically meaningful because it regards as treatment failures those whose symptoms do not remit within the four month time frame of the study. Secondary outcome measures will include health related quality of life metrics. Exploratory (hypothesis-generating) analyses will compare the time to progression to sustained generalized myasthenia gravis in the two treatment groups as well as an examination of the safety and efficacy of the high-dose prednisone strategy.